The association between adiponectin/leptin ratio and diabetes type: the SEARCH for Diabetes in Youth Study
Maahs DM , Hamman RF , D'Agostino R Jr , Dolan LM , Imperatore G , Lawrence JM , Marcovina SM , Mayer-Davis EJ , Pihoker C , Dabelea D . J Pediatr 2009 155 (1) 133-5, 135 e1 We tested the association of adiponectin/leptin ratio with diabetes type after adjusting for multiple factors in 1156 youths with newly diagnosed diabetes in the SEARCH study. Although adiponectin/leptin ratio is associated with diabetes type in youth, it is due to differences in adiponectin, but not leptin levels. |
Associations between smoking cessation and anxiety and depression among U.S. adults
McClave AK , Dube SR , Strine TW , Kroenke K , Caraballo RS , Mokdad AH . Addict Behav 2009 34 491-7 Many studies have shown a relationship between smoking and depression. However, few studies have examined the association between current depression and smoking and even fewer used large cross-sectional data to support these findings. Using the 2006 Behavioral Risk Factor Surveillance System data (n=248,800), we compared rates of lifetime depression, lifetime anxiety, current depression, and current depressive symptoms among smokers who unsuccessfully attempted to quit (unsuccessful quitters), former smokers (successful quitters), and smokers who made no attempts to quit (non-quitters). Unsuccessful quitters experienced more lifetime depression and anxiety than non-quitters (OR=1.2; 95% CI, 1.0-1.4), whereas successful quitters experienced less (OR=0.7, 95% CI, 0.6-0.8). Current depression prevalence was 14.3% among non-quitters, 18.8% among unsuccessful quitters, and 8.0% among successful quitters. On average, unsuccessful quitters also experienced more days of depressive symptoms during the previous month than either non-quitters or successful quitters. Our results suggest that smokers who attempt to quit unsuccessfully may experience lifetime depression as well as current depression at a higher rate than other smokers and former smokers. |
Care of long-term cancer survivors: physicians seen by Medicare enrollees surviving longer than 5 years
Pollack LA , Adamache W , Ryerson AB , Eheman CR , Richardson LC . Cancer 2009 115 (22) 5284-95 BACKGROUND: Studies have shown that follow-up care for cancer patients differs by physician specialty, and that coordination between specialists and generalists results in better care. Little is known, however, regarding which specialties of physicians provide care to long-term cancer survivors. METHODS: The authors used Surveillance, Epidemiology, and End Results data from 1992 through 1997 that were linked to 1997-2003 Medicare data to identify persons diagnosed >5 years earlier with bladder, female breast, colorectal, prostate, or uterine cancer. Physician specialties were assigned by combining Medicare data with the American Medical Association Masterfile and the Unique Physician Identification Number Registry. The percentage of long-term survivors who visited physicians of interest was determined by analyzing Medicare outpatient claims submitted 6 to 12 years after initial diagnosis. RESULTS: Over the entire study period, 46% of female breast cancer survivors, 26% of colorectal cancer survivors, and 14% of prostate cancer survivors saw hematologists/oncologists. Radiation oncologists were seen by 11%, 2%, and 14% of breast, colorectal, and prostate cancer survivors, respectively. Survivors also sought care from specialists related to their cancer: 19% of breast cancer survivors had a cancer-coded visit with a surgeon, 26% of colorectal cancer survivors visited a gastroenterologist, and 68% of prostate cancer survivors visited a urologist. The percentage of survivors who visited cancer and cancer-related physicians declined each year. In contrast, nearly 75% of female breast, colorectal, and prostate cancer survivors saw primary care providers, and these percentages did not decrease annually. CONCLUSIONS: The findings of the current study underscore the need to include both primary care providers and cancer-related specialists in education and guidelines regarding cancer survivorship. Cancer 2009. (c) 2009 American Cancer Society. |
Factors explaining excess stroke prevalence in the US Stroke Belt
Liao Y , Greenlund KJ , Croft JB , Keenan NL , Giles WH . Stroke 2009 40 (10) 3336-41 BACKGROUND AND PURPOSE: Higher risk and burden of stroke have been observed within the southeastern states (the Stroke Belt) compared with elsewhere in the United States. We examined reasons for these disparities using a large data set from a nationwide cross-sectional study. METHODS: Self-reported data from the 2005 and 2007 Behavioral Risk Factor Surveillance System were used (n=765 368). The potential contributors for self-reported stroke prevalence (n=27 962) were demographics (age, sex, geography, and race/ethnicity), socioeconomic status (education and income), common risk factors (smoking and obesity), and chronic diseases (hypertension, diabetes, and coronary heart disease). Multivariate logistic regression was used in the analysis. RESULTS: The age- and sex-adjusted OR comparing self-reported stroke prevalence in the 11-state Stroke Belt versus non-Stroke Belt region was 1.25 (95% CI, 1.19 to 1.31). Unequal black/white distribution by region accounted for 20% of the excess prevalence in the Stroke Belt (OR reduced to 1.20; 1.15 to 1.26). Approximately one third (32%) of the excess prevalence was accounted either by socioeconomic status alone or by risk factors and chronic disease alone (OR, 1.12). The OR was further reduced to 1.07 (1.02 to 1.13) in the fully adjusted logistic model, a 72% reduction. CONCLUSIONS: Differences in socioeconomic status, risk factors, and prevalence of common chronic diseases account for most of the regional differences in stroke prevalence. |
What is the optimal therapy for patients with H5N1 influenza?
White NJ , Webster RG , Govorkova EA , Uyeki TM . PLoS Med 2009 6 (6) e1000091 BACKGROUND TO THE DEBATE: In a 2007 article in PLoS Medicine[10], Holger J. Schunemann and colleagues described a new process used by the World Health Organization for rapidly developing clinical management guidelines in emergency situations. These situations include outbreaks of emerging infectious diseases. The authors discussed how they developed such a "rapid advice" guideline for the pharmacological management of avian influenza A (H5N1) virus infection. The guideline recommends giving the antiviral drug oseltamivir at a dose of 75 mg twice daily for five days. In this Debate, Nicholas White argues that such dosing is inadequate, Robert Webster and Elena Govorkova say that combination antiviral therapy should be used, and Tim Uyeki reminds us that clinical care of patients with H5N1 entails much more than antiviral treatment. These issues may also apply to therapy of patients hospitalized with severe disease due to novel swine-origin influenza A (H1N1) virus infection. |
Antibiotic prescription rates for acute respiratory tract infections in US ambulatory settings
Grijalva CG , Nuorti JP , Griffin MR . JAMA 2009 302 (7) 758-66 CONTEXT: During the 1990s, antibiotic prescriptions for acute respiratory tract infection (ARTI) decreased in the United States. The sustainability of those changes is unknown. OBJECTIVE: To assess trends in antibiotic prescriptions for ARTI. DESIGN, SETTING, AND PARTICIPANTS: The National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey data (1995-2006) were used to examine trends in antibiotic prescription rates by antibiotic indication and class. Annual survey data and census denominators were combined in 2-year intervals for rate calculations. MAIN OUTCOME MEASURES: National annual visit rates and antibiotic prescription rates for ARTI, including otitis media (OM) and non-ARTI. RESULTS: Among children younger than 5 years, annual ARTI visit rates decreased by 17% (95% confidence interval [CI], 9%-24%), from 1883 per 1000 population in 1995-1996 to 1560 per 1000 population in 2005-2006, primarily due to a 33% (95% CI, 22%-43%) decrease in OM visit rates (950 to 634 per 1000 population, respectively). This decrease was accompanied by a 36% (95% CI, 26%-45%) decrease in ARTI-associated antibiotic prescriptions (1216 to 779 per 1000 population). Among persons aged 5 years or older, ARTI visit rates remained stable but associated antibiotic prescription rates decreased by 18% (95% CI, 6%-29%), from 178 to 146 per 1000 population. Antibiotic prescription rates for non-OM ARTI for which antibiotics are rarely indicated decreased by 41% (95% CI, 22%-55%) and 24% (95% CI, 10%-37%) among persons younger than 5 years and 5 years or older, respectively. Overall, ARTI-associated prescription rates for penicillin, cephalosporin, and sulfonamide/tetracycline decreased. Prescription rates for azithromycin increased and it became the most commonly prescribed macrolide for ARTI and OM (10% of OM visits). Among adults, quinolone prescriptions increased. CONCLUSIONS: Overall antibiotic prescription rates for ARTI decreased, associated with fewer OM visits in children younger than 5 years and with fewer prescriptions for ARTI for which antibiotics are rarely indicated. However, prescription rates for broad-spectrum antibiotics increased significantly. |
Can we "hedge" against the development of antiviral resistance among pandemic influenza viruses?
Shay DK , Ridenhour BJ . PLoS Med 2009 6 (6) e1000103 David K. Shay and Benjamin Ridenhour discuss a modeling study predicting that stockpiling a secondary antiviral for use early in a flu pandemic can forestall resistance to the primary stockpiled drug. |
Clinical features, outcomes, and costs of a conjunctivitis outbreak caused by the ST448 strain of Streptococcus pneumoniae
Zegans ME , Sanchez PA , Likosky DS , Allar RT , Martin M , Schwartzman JD , Pryor JH , Turco JH , Whitney CG . Cornea 2009 28 (5) 503-9 PURPOSE: An outbreak of pneumococcal conjunctivitis occurred at Dartmouth College in 2002. We describe the clinical features, outcomes, and costs associated with this outbreak. METHODS: Six hundred ninety-eight students were diagnosed with conjunctivitis; culture of conjunctival discharge was obtained for 254. A screening protocol was used to evaluate 67 patients. A retrospective survey was offered to all 698 cases and follow-up clinical examination to all patients with culture-confirmed infection (n = 110). Local ophthalmology offices were contacted to develop a cost analysis. The college health service provided conjunctivitis data for nonoutbreak years. RESULTS: Of 67 patients evaluated using the screening protocol, findings associated with culture-confirmed Streptococcus pneumoniae conjunctivitis (P < 0.01) were red eye visible from 2 feet, any type of conjunctival discharge, obscuration of tarsal conjunctival blood vessels, and chemosis. Two hundred thirty-two students responded to our retrospective survey; 89% reported bilateral eye involvement; 96% received topical antibiotics and noted symptom improvement within 3 days of treatment. No ocular sequelae were identified as a result of this infection. No recurrent outbreaks have occurred at Dartmouth since the initial event. The estimated cost of this outbreak including evaluations, cultures, and antibiotics ranged from $66,468 to $120,583. CONCLUSIONS: The ST448 strain of S. pneumoniae caused a disruptive outbreak of conjunctivitis at Dartmouth College. A screening protocol was effective at identifying culture-positive cases. Although most culture-positive patients experienced bilateral conjunctivitis, the clinical course was mild with quick resolution of symptoms after initiating antibiotics and no ocular sequelae. |
Efficacy of an HIV/STI prevention intervention for black men who have sex with men: findings from the Many Men, Many Voices (3MV) project
Wilton L , Herbst JH , Coury-Doniger P , Painter TM , English G , Alvarez ME , Scahill M , Roberson MA , Lucas B , Johnson WD , Carey JW . AIDS Behav 2009 13 (3) 532-44 Black men who have sex with men (MSM) in the United States experience disproportionately high rates of HIV and other sexually transmitted infections (STIs); however, the number of evidence-based interventions for Black MSM is limited. This study evaluated the efficacy of Many Men, Many Voices (3MV), a small-group HIV/STI prevention intervention developed by Black MSM-serving community-based organizations and a university-based HIV/STI prevention and training program. The study sample included 338 Black MSM of HIV-negative or unknown HIV serostatus residing in New York city. Participants were randomly assigned to the 3MV intervention condition (n = 164) or wait-list comparison condition (n = 174). Relative to comparison participants, 3MV participants reported significantly greater reductions in any unprotected anal intercourse with casual male partners; a trend for consistent condom use during receptive anal intercourse with casual male partners; and significantly greater reductions in the number of male sex partners and greater increases in HIV testing. This study is the first randomized trial to demonstrate the efficacy of an HIV/STI prevention intervention for Black MSM. |
Evidence based interventions for preventing HIV transmission: commentary on Rotheram-Borus et al. (2009)
Collins CB Jr . AIDS Behav 2009 13 (3) 414-9; discussion 420-3 In their article “Family Wellness, Not HIV Prevention” Rotheram-Borus et al. (2009) state that “sustained improvements in global health require creating a prevention infrastructure to meet the multiple health challenges experienced by local communities.” They then identify four fundamental shifts in HIV and disease prevention. This commentary points out that these shifts are not new but are already being implemented, and some lessons learned indicate they are not complete solutions but strategies that can be integrated with other approaches to the delivery of behavioral and biomedical prevention. | The four suggested shifts are discussed in the following sections. |
Factors associated with positive tuberculin skin test results among HIV-infected persons in Orel Oblast, Russia
Vitek E , Gusseinova N , Laricheva N , Vasiliev S , Molotilov V , Sofronova R , Kazionny B , Cegielski P , Nguyen ML , Nelson L , Agerton T , Wells C . Int J Tuberc Lung Dis 2009 13 (7) 829-35 BACKGROUND: The treatment of persons living with human immunodeficiency virus/acquired immune-deficiency syndrome (PLWHAs) for latent tuberculosis infection (LTBI) reduces tuberculosis (TB) morbidity. Despite a high TB burden and an expanding human immunodeficiency virus epidemic, Russia had limited data on the utility of the tuberculin skin test (TST) for LTBI diagnosis in PLWHAs. OBJECTIVE: To determine the prevalence and predictors of positive TSTs in PLWHAs in Orel Oblast. METHODS: A total of 150 consenting PLWHAs being followed up at the AIDS Center were administered a TST and a questionnaire for risk factors for LTBI. A positive TST result was defined as >or=5 mm induration. RESULTS: Of the 150 subjects, 67% were male and 74% were aged <30 years. Of the PLWHAs tested, 26% had a positive TST result, while among PLWHAs with CD4(+) >500 cells/ml, 36% were TST-positive. TST positivity varied inversely with CD4(+) cell count. Among PLWHAs with a history of injection drug use, the primary risk factor for HIV, 29 (31.9%) were positive. CONCLUSIONS: A high proportion of tested PLWHAs had a positive TST and could benefit from preventive therapy (PT) to reduce the risk of TB. A TB control programme in Russia should therefore include TST screening among PLWHAs and PT, besides active TB case finding and treatment. |
Increasing proportions of advanced pulmonary tuberculosis in the United States: are delays in diagnosis on the rise?
Wallace RM , Kammerer JS , Iademarco MF , Althomsons SP , Winston CT , Navin TR . Am J Respir Crit Care Med 2009 180 (10) 1016-22 INTRODUCTION: Delays in the diagnosis of tuberculosis can result in progression to advanced disease. Pulmonary tuberculosis patients with advanced disease are more likely to transmit disease and fail treatment. METHODS: Pulmonary tuberculosis cases in persons >15 years of age reported to the U.S. National Tuberculosis Surveillance System with advanced disease (cavitation on chest radiograph and acid-fast-bacilli smear-positive sputum result) were compared with those without advanced disease using trend and binomial regression analysis. RESULTS: There were 35,584 cases of advanced pulmonary tuberculosis (APT) and 125,077 cases of non-APT reported from 1993 through 2006. Proportions of pulmonary tuberculosis cases with APT increased from 18.5% in 1993 to 26.1% in 2006, and the increase in the proportion of APT was most notable for national tuberculosis rates below 6.6 per 100,000. At the county level, the association between APT and low tuberculosis incidence has grown incrementally stronger since 2000. The proportion of APT increased greatest among whites (65.4%), the employed (63.3%), and the U.S. born (59.2%). The prevalence of APT was 44% greater among persons with multidrug-resistant tuberculosis compared to those without it. CONCLUSION: This study highlights the need for tuberculosis diagnosis at early stages of the disease to minimize APT and decrease the risk of transmission. Additional efforts should concentrate on reducing time to treatment initiation in low-incidence areas and among groups traditionally seen as being at low-risk for tuberculosis disease. |
Investigation of a mumps outbreak among university students with two measles-mumps-rubella (MMR) vaccinations, Virginia, September-December 2006
Rota JS , Turner JC , Yost-Daljev MK , Freeman M , Toney DM , Meisel E , Williams N , Sowers SB , Lowe L , Rota PA , Nicolai LA , Peake L , Bellini WJ . J Med Virol 2009 81 (10) 1819-1825 Following the clinical diagnosis of the first case of mumps on September 22, 2006 at the University of Virginia (UVA), 52 suspected cases were identified through active surveillance for mumps by the end of December 2006. Samples were collected from 47 students who presented with parotitis despite a documented history of two doses of measles, mumps, and rubella (MMR) vaccine. Six of 47 serum samples (13%) were positive for mumps IgM, and 46/47 specimens were positive for mumps IgG. Endpoint titration of acute phase serum samples from laboratory-confirmed cases did not provide evidence that elevated serum IgG is a consistent marker for infection among cases due to secondary vaccine failure. Buccal swab samples from 39 of the 47 students were tested by real-time reverse transcription-polymerase chain reaction (RT-PCR) and/or viral culture. Mumps virus or mumps RNA was detected in 12 of 39 buccal samples (31%). Genetic analysis of the virus from the outbreak at UVA indicated that the outbreak was not linked to the large mumps outbreak in the Midwestern US that occurred earlier in 2006. Our findings support the use of viral detection to improve laboratory diagnosis of mumps among persons who have received two doses of MMR. J. Med. Virol. 81:1819-1825, 2009. (c) 2009 Wiley-Liss, Inc. |
Public health and drought
Kalis MA , Miller MD , Wilson RJ . J Environ Health 2009 72 (1) 10-1 At the most basic conceptual level, | drought is a natural phenomenon in | which levels of rainfall or other types | of precipitation are lower than average for | an extended period of time, resulting in | inadequate water supply. To truly understand drought and its effect on people and | the environment, including human health | impacts, one must also consider differences | in geographic regions, local water demand, | and variables such as a community’s ability to adapt to water shortages and state | and local policies that regulate water supply (www.drought.unl.edu). For instance, | a significant amount of annual rainfall in | the southwestern U.S could be considered | a drought in the Northwest. The photo at | the top of page 11 illustrates recent conditions in the southeastern United States. As | a readily available supply of safe water is | a prerequisite for public health, droughts | have potential public health significance | and understanding the relationship between the two is an important first step in | examining potential associations. |
Association of self-reported leisure-time physical inactivity with particulate matter 2.5 air pollution
Wen XJ , Balluz LS , Shire JD , Mokdad AH , Kohl HW . J Environ Health 2009 72 (1) 40-4; quiz 45 This study examines the association between annual levels of particulate matter (PM) and self-reported leisure-time physical inactivity (LTPI) in the Behavioral Risk Factor Surveillance System (BRFSS) among 63,290 survey respondents who participated in the 2001 BRFSS from 142 counties in the U.S. The average prevalence of self-reported LTPI was about 24.9% (SE = 0.3%), LTPI prevalence was positively associated with annual mean of PM.5 concentration (p < .0001). The authors demonstrate that LTPI was associated with PM2.5 pollution with statistical significance with and without adjustment for covariates (adjusted odds ration [OR] = 1.16; 95% CI: [confidence interval] 1.06-1.27). This study suggests that ambient PM2.5 air pollution is associated independently with LTPI. PM2.5 pollution and physical inactivity are both risk factors of chronic diseases. Therefore, it is important for environmental officials to implement measures to reduce ambient air pollution while public health officials simultaneously promote regular physical activity by encouraging the general public to remain physically active. |
Demographic variability, vaccination, and the spatiotemporal dynamics of rotavirus epidemics
Pitzer VE , Viboud C , Simonsen L , Steiner C , Panozzo CA , Alonso WJ , Miller MA , Glass RI , Glasser JW , Parashar UD , Grenfell BT . Science 2009 325 (5938) 290-4 Historically, annual rotavirus activity in the United States has started in the southwest in late fall and ended in the northeast 3 months later; this trend has diminished in recent years. Traveling waves of infection or local environmental drivers cannot account for these patterns. A transmission model calibrated against epidemiological data shows that spatiotemporal variation in birth rate can explain the timing of rotavirus epidemics. The recent large-scale introduction of rotavirus vaccination provides a natural experiment to further test the impact of susceptible recruitment on disease dynamics. The model predicts a pattern of reduced and lagged epidemics postvaccination, closely matching the observed dynamics. Armed with this validated model, we explore the relative importance of direct and indirect protection, a key issue in determining the worldwide benefits of vaccination. |
Genetic characterization of Chinese measles vaccines by analysis of complete genomic sequences
Zhang Y , Zhou J , Bellini WJ , Xu W , Rota PA . J Med Virol 2009 81 (8) 1477-83 The complete genomic sequences of two Chinese measles vaccine viruses, Shanghai-191 (S-191) and Changchun-47 (C-47), were determined and compared to the sequences of other measles vaccine strains as well as the prototype measles strain, Edmonston wild-type (Edwt). Compared to Edwt, S-191 and C-47 had 49 and 43 nucleotide changes, respectively. These differences were found at 52 nucleotide positions that were not found in other vaccine strains. Phylogenetic analysis of the all of the available genomic sequences for measles vaccines showed that S-191 and C-47 were most closely related to the Leningrad-4 strain. S-191 and C-47 shared conserved vaccine virus-specific amino acid changes in the phosphoprotein (P), V, C, matrix (M), and hemagglutinin (H) that could represent important targets for future studies aimed at understanding the molecular basis of attenuation. In addition, S-191 and C-47 had several unique amino acid changes including 13 positions that differed from Edwt. This is the first comparison of the complete genomic sequences of Chinese measles vaccines to the sequences of other vaccine strains. |
Genetic determinants of sensitivity to beryllium in mice
Tarantino-Hutchison LM , Sorrentino C , Nadas A , Zhu Y , Rubin EM , Tinkle SS , Weston A , Gordon T . J Immunotoxicol 2009 6 (2) 130-5 Chronic beryllium disease (CBD), an irreversible, debilitating granulomatous lung disease is caused by exposure to beryllium. This occupational hazard occurs in primary production and machining of Be-metal, BeO, beryllium - containing alloys, and other beryllium products. CBD begins as an MHC Class II-restricted, T(H)1 hypersensitivity, and the Human Leukocyte Antigen, HLA-DPB1E(69), is associated with risk of developing CBD. Because inbred strains of mice have not provided good models of CBD to date, three strains of HLA-DPB1 transgenic mice in an FVB/N background were developed; each contains a single allele of HLA-DPB1 that confers a different magnitude of risk for chronic beryllium disease: HLA-DPB1*0401 (OR approximately 0.2), HLA-DPB1*0201 (OR approximately 3), and HLA-DPB1*1701 (OR approximately 46). The mouse ear swelling test (MEST) was employed to determine if these different alleles would support a hypersensitivity response to beryllium. Mice were first sensitized on the back and subsequently challenged on the ear. In separate experiments, mice were placed into one of three groups (sensitization/challenge): C/C, C/Be, and Be/Be. In the HLA-DPB1*1701 mice, the strain with the highest risk transgene, the Be/Be group was the only group that displayed significant maximum increased ear thickness of 19.6% +/- 3.0% over the baseline measurement (p < 0.05). No significant changes were observed in the other transgenic strains for any treatment condition. In addition, inter-strain differences in response to beryllium in seven inbred strains were investigated through use of the MEST, these included: FVB/N, AKR, Balb/c, C3H/HeJ, C57/BL6, DBA/2, and SJL/J. The FVB/N strain was least responsive, while the SJL/J and C57/BL6 strains were the highest responders. Our results suggest that the HLA-DPB1*1701 transgene product is an important risk factor for induction of the beryllium-sensitive phenotype. This model should be a useful tool for investigating beryllium sensitization. |
Genetic inactivation of poliovirus infectivity by increasing the frequencies of CpG and UpA dinucleotides within and across synonymous capsid region codons
Burns CC , Campagnoli R , Shaw J , Vincent A , Jorba J , Kew O . J Virol 2009 83 (19) 9957-69 Replicative fitness of poliovirus can be systematically modulated by replacement of preferred capsid region codons with synonymous unpreferred codons. To determine the key genetic contributors to fitness reduction, we introduced different sets of synonymous codons into the capsid region of an infectious clone derived from the type 2 prototype strain, MEF-1. Replicative fitness in HeLa cells, measured by plaque areas and virus yields in single-step growth experiments, decreased sharply with increased frequencies of the dinucleotides CpG (suppressed in higher eukaryotes and most RNA viruses) and UpA (suppressed nearly universally). Replacement of MEF-1 capsid codons with the corresponding codons from another type 2 prototype strain (Lansing), a randomization of MEF-1 synonymous codons, increased %G+C (without increased CpG), and reductions in the effective number of codons used (NC) had much smaller individual effects on fitness. Poliovirus fitness was reduced to the threshold of viability when CpG and UpA dinucleotides were saturated within and across synonymous codons of a capsid region interval representing only approximately 9% of the total genome. Codon replacements were associated with moderate decreases in total virion production but large decreases in the specific infectivities of intact poliovirions and viral RNAs. Replication of codon-replacement viruses, but not MEF-1, was temperature sensitive at 39.5 degrees C. Synthesis and processing of viral intracellular proteins were largely unaltered in most codon-replacement constructs. Replacement of natural codons with synonymous codons with increased frequencies of CpG and UpA dinucleotides may offer a general approach to the development of attenuated vaccines with well-defined antigenicities and very high genetic stabilities. |
Gay identity-related factors and sexual risk among men who have sex with men in San Francisco
Flores SA , Mansergh G , Marks G , Guzman R , Colfax G . AIDS Educ Prev 2009 21 (2) 91-103 This study explored the relationship between gay identity-related factors (gay community involvement, gay bar attendance, gay identity importance, and self-homophobia) and unprotected anal sex (UA) in the past 3 months among men who have sex with men (MSM) of three different race/ethnicity groups. Four hundred eighty-three MSM (mean age 34) were recruited in the San Francisco Bay Area (33% African American, 34% Latino and 33% White). Compared with White MSM, African American and Latino MSM were less likely to identify as gay, and to attend gay bars/clubs, and more likely to report self-homophobia. Just over one third of the sample reported UA (did not vary by race). Gay community involvement was associated with receptive UA with all partners (adjusted odds ratio [AOR = 1.30, 95% Confidence Interval (CI) = 1.06-1.60). Gay bar attendance was associated with insertive UA with all partners (AOR = 1.20, 95% CI = 1.01-1.43) and with HIV-discordant partners (AOR = 1.35, 95% CI = 1.08-1.69). Implications for prevention include addressing community norms and encouraging alternatives to bars as settings in which to meet and socialize with other MSM. |
A peer-led HIV counselling and testing programme for the deaf in Kenya
Taegtmeyer M , Hightower A , Opiyo W , Mwachiro L , Henderson K , Angala P , Ngare C , Marum E . Disabil Rehabil 2009 31 (6) 508-14 PURPOSE: To describe and evaluate the establishment of the first VCT services for the Deaf in Africa. METHOD: Operational research methods were used to document programme establishment. The demographics of deaf VCT clients were compared with hearing clients at the same sites as well as where clients had learned of the service, HIV risks, and HIV test results. Univariate and multivariate analyses were used. RESULTS: During the two year period (January 2004 to December 2005) 1709 Deaf and 1649 hearing clients were seen at three Deaf VCT sites. The majority of Deaf clients in this sample learned of the services through the peer education programme. Data indicate that Deaf VCT clients are as much at risk of HIV from sexual transmission as their hearing counterparts and that Deaf persons seeking VCT services have an HIV prevalence of 7%, similar to the national rate of 6.7%. CONCLUSIONS: The Deaf in Kenya are at risk of HIV and there is an urgent need for Deaf-friendly HIV services, supplemented by peer education programmes. This is the first published report describing HIV services run by the Deaf for the Deaf in the developing world. |
Effects of an Internet-based intervention for HIV prevention: the Youthnet trials
Bull S , Pratte K , Whitesell N , Rietmeijer C , McFarlane M . AIDS Behav 2009 13 (3) 474-87 Youth use the Internet and computers in unprecedented numbers. We have yet to identify interventions that can reach and retain large numbers of diverse youth online and demonstrate HIV prevention efficacy. We tested a single session condom promotion Internet intervention for 18-24 year olds in two RCTs: one sample recruited online and one recruited in clinics. All study elements were carried out on the Internet. Using repeated measures structural equation models we analyzed change in proportion of sex acts protected by condoms (PPA) over time. Among sexually active youth in the Internet sample, persons exposed to the intervention had very slight increases in condom norms, and this was the only factor impacting PPA. We saw no intervention effects in the clinic sample. Internet-based interventions need to be more intensive to see greater effects. We need to do more to reach high risk youth online and keep their attention for multiple sessions. |
Evaluating nurses' implementation of an infant-feeding counseling protocol for HIV-infected mothers: The BAN Study in Lilongwe, Malawi
Ferguson YO , Eng E , Bentley M , Sandelowski M , Steckler A , Randall-David E , Piwoz EG , Zulu C , Chasela C , Soko A , Tembo M , Martinson F , Tohill BC , Ahmed Y , Kazembe P , Jamieson DJ , van der Horst C , UNC Project BAN Study Team . AIDS Educ Prev 2009 21 (2) 141-55 A process evaluation of nurses' implementation of an infant-feeding counseling protocol was conducted for the Breastfeeding, Antiretroviral and Nutrition (BAN) Study, a prevention of mother-to-child transmission of HIV clinical trial in Lilongwe, Malawi. Six trained nurses counseled HIV-infected mothers to exclusively breastfeed for 24 weeks postpartum and to stop breastfeeding within an additional four weeks. Implementation data were collected via direct observations of 123 infant feeding counseling sessions (30 antenatal and 93 postnatal) and interviews with each nurse. Analysis included calculating a percent adherence to checklists and conducting a content analysis for the observation and interview data. Nurses were implementing the protocol at an average adherence level of 90% or above. Although not detailed in the protocol, nurses appropriately counseled mothers on their actual or intended formula milk usage after weaning. Results indicate that nurses implemented the protocol as designed. Results will help to interpret the BAN Study's outcomes. |
Postlicensure safety surveillance for quadrivalent human papillomavirus recombinant vaccine
Slade BA , Leidel L , Vellozzi C , Woo EJ , Hua W , Sutherland A , Izurieta HS , Ball R , Miller N , Braun MM , Markowitz LE , Iskander J . JAMA 2009 302 (7) 750-7 CONTEXT: In June 2006, the Food and Drug Administration licensed the quadrivalent human papillomavirus (types 6, 11, 16, and 18) recombinant vaccine (qHPV) in the United States for use in females aged 9 to 26 years; the Advisory Committee on Immunization Practices then recommended qHPV for routine vaccination of girls aged 11 to 12 years. OBJECTIVE: To summarize reports to the Vaccine Adverse Event Reporting System (VAERS) following receipt of qHPV. DESIGN, SETTING, AND PARTICIPANTS: Review and describe adverse events following immunization (AEFIs) reported to VAERS, a national, voluntary, passive surveillance system, from June 1, 2006, through December 31, 2008. Additional analyses were performed for some AEFIs in prelicensure trials, those of unusual severity, or those that had received public attention. Statistical data mining, including proportional reporting ratios (PRRs) and empirical Bayesian geometric mean methods, were used to detect disproportionality in reporting. MAIN OUTCOME MEASURES: Numbers of reported AEFIs, reporting rates (reports per 100,000 doses of distributed vaccine or per person-years at risk), and comparisons with expected background rates. RESULTS: VAERS received 12 424 reports of AEFIs following qHPV distribution, a rate of 53.9 reports per 100,000 doses distributed. A total of 772 reports (6.2% of all reports) described serious AEFIs, including 32 reports of death. The reporting rates per 100,000 qHPV doses distributed were 8.2 for syncope; 7.5 for local site reactions; 6.8 for dizziness; 5.0 for nausea; 4.1 for headache; 3.1 for hypersensitivity reactions; 2.6 for urticaria; 0.2 for venous thromboembolic events, autoimmune disorders, and Guillain-Barre syndrome; 0.1 for anaphylaxis and death; 0.04 for transverse myelitis and pancreatitis; and 0.009 for motor neuron disease. Disproportional reporting of syncope and venous thromboembolic events was noted with data mining methods. CONCLUSIONS: Most of the AEFI rates were not greater than the background rates compared with other vaccines, but there was disproportional reporting of syncope and venous thromboembolic events. The significance of these findings must be tempered with the limitations (possible underreporting) of a passive reporting system. |
Reduction in hepatitis B virus seroprevalence among U.S.-born children of foreign-born Asian parents-Benefit of universal infant hepatitis B vaccination
Shuler CM , Fiore AE , Neeman R , Bell BP , Kuhnert W , Watkins S , Kilgour K , Arnold KE . Vaccine 2009 27 (43) 5942-7 We demonstrate that after implementation of recommendations for universal infant hepatitis B vaccination, HBV infection prevalence among children of foreign-born Asian parents in Georgia declined dramatically; horizontal transmission of infection within households has occurred infrequently; and the vast majority of infants and children have received the recommended hepatitis B vaccinations. These results provide evidence of the success of the hepatitis B infant vaccination program and highlight its potential impact on reducing chronic HBV infection morbidity and mortality among U.S. populations at high risk. |
Considerations for the definition, measurement, consequences, and prevention of dating violence victimization among adolescent girls
Teten AL , Ball B , Valle LA , Noonan R , Rosenbluth B . J Womens Health (Larchmt) 2009 18 (7) 923-7 Violence experienced by adolescent girls from their dating partners poses considerable threat to their health and well-being. This report provides an overview of the prevalence and consequences of heterosexual teen dating violence and highlights the need for comprehensive prevention approaches to dating violence. We also discuss some considerations and future directions for the study and prevention of dating violence. We begin with a discussion of the definition of dating violence and also discuss measurement concerns and the need for evaluation of prevention strategies. Although women and men of all ages may be the victims or perpetrators, male-to-female dating violence experienced by adolescent girls is the main focus of this article. We incorporate research regarding girls' perpetration of dating violence where appropriate and as it relates to prevention. |
An innovative approach to serving the needs of IPV survivors: description of a CDC-Funded study examining the Volunteers of America Home Free rent assistance program
Niolon PH , Rollins CM , Glass N , Billhardt K , Connor-Smith J , Baker C . J Womens Health (Larchmt) 2009 18 (6) 775-8 The purpose of this paper is to describe a CDC-funded study examining the effectiveness and cost-effectiveness of the Volunteers of America Home Free program, an innovative program that offers survivors of intimate partner violence (IPV) permanent housing rent assistance coupled with client-centered advocacy. We briefly discuss the challenges and barriers faced by women who try to separate from abusive partners and who have an immediate need for housing, describe the innovative approach to service provision adopted by the Volunteers of America Home Free program in Portland, Oregon, and describe the CDC-funded cooperative agreement to compare the effectiveness and cost-effectiveness of this approach with the usual housing services available to women fleeing abusive relationships. |
Morphology of single-wall carbon nanotube aggregates generated by electrospray of aqueous suspensions
Ku BK , Kulkarni P . J Nanopart Res 2009 11 (6) 1393-1403 Airborne single-wall carbon nanotubes (SWCNTs) have a high tendency to agglomerate due to strong interparticle attractive forces. The SWCNT agglomerates generally have complex morphologies with an intricate network of bundles of nanotubes and nanoropes, which limits their usefulness in many applications. It is thus desirable to produce SWCNT aerosol particles that have well-defined, unagglomerated fibrous morphologies. We present a method to generate unagglomerated, fibrous particles of SWCNT aerosols using capillary electrospray of aqueous suspensions. The effects of the operating parameters of capillary electrospray such as strength of buffer solution, capillary diameter, flow rate, and colloidal particle concentration on the size distributions of SWCNT aerosols were investigated. Results showed that electrospray from a suspension of higher nanotube concentration produced a bimodal distribution of SWCNT aerosols. Monodisperse SWCNT aerosols below 100 nm were mostly non-agglomerated single fibers, while polydisperse aerosols larger than 100 nm had two distinct morphologies: a ribbon shape and the long, straight fiber. Possible mechanisms are suggested to explain the formation of the different shapes, which could be used to produce SWCNT aerosols with different morphologies. |
Neurotoxin gene clusters in Clostridium botulinum type Ab strains
Luquez C , Raphael BH , Maslanka SE . Appl Environ Microbiol 2009 75 (19) 6094-101 There is limited knowledge of the neurotoxin gene diversity among Clostridium botulinum type Ab strains. Only the sequences of the bont/A and bont/B genes in C. botulinum type Ab strain CDC1436, and the sequence of the bont/B gene of C. botulinum type Ab strain CDC588 have been reported. In this study, we sequenced the entire bont/A and bont/B associated neurotoxin gene clusters of C. botulinum type Ab strain CDC41370, and the bont/A gene of strain CDC588. In addition, we analyzed the organization of the neurotoxin gene clusters in strains CDC588 and CDC1436. The bont/A nucleotide sequence of strain CDC41370 differed from the known bont/A subtypes A1 - A4 by 2 to 7%, and the predicted amino acid sequence differed by 4% to 14%. The bont/B nucleotide sequence in strain CDC41370 showed 99.7% identity to the sequence of subtype B1. The bont/A nucleotide sequence of strain CDC588 was 99.9% identical to subtype A1. Although all of the C. botulinum type Ab strains analyzed contained the two sets of neurotoxin clusters similar to what has been found in other bivalent strains, the intergenic spacing of p21-orfX1 and orfX2-orfX3 varied among these strains. The type Ab strains examined in this study had differences in their toxin gene cluster composition and bont/A and /B nucleotide sequences, suggesting that they may have arisen from separate recombination events. |
Paravahlkampfia francinae n. sp. masquerading as an agent of primary amoebic meningoencephalitis
Visvesvara GS , Sriram R , Qvarnstrom Y , Bandyopadhyay K , Da Silva AJ , Pieniazek NJ , Cabral GA . J Eukaryot Microbiol 2009 56 (4) 357-66 Paravahlkampfia francinae n. sp., a new species of the free-living amoeba genus Paravahlkampfia, designated as CDC:V595, was isolated from the cerebrospinal fluid of a patient with headache, sore throat, and vomiting, typical symptoms of primary amoebic meningoencephalitis (PAM) caused by Naegleria fowleri. The isolate grew at 33 degrees C, 37 degrees C, 40 degrees C, and 42 degrees C and destroyed mammalian cell cultures. However, it did not kill young mice upon intranasal inoculation. P. francinae does not produce flagellates and does not grow on agar plates coated with Gram-negative bacteria such as Escherichia coli, the usual food source of Paravahlkampfia ustiana, the type species of the genus. The trophozoite at light microscopy exhibited eruptive locomotion and possessed a single vesicular nucleus. Ultrastructurally, the trophozoites had numerous mitochondria with discoidal cristae but did not have a Golgi apparatus. The trophozoites differentiated into cysts after consuming most of the monolayer. The cyst had an inner well-differentiated endocyst and an outer thin, wrinkled, and wavy ectocyst with no pores. During excystation trophozoites ruptured the cyst wall and emerged from the cysts. A unique feature seen in the cysts was the presence of bacterial endosymbionts, both in the endoplasm and within the cyst wall. Full-length sequencing analysis of the 18S and 5.8S RNA genes of P. francinae showed that they were distinct from those of other Paravahlkampfia species. The patient recovered within a few days indicating that some of the previously reported cases of PAM that survived may have been due to P. francinae. |
Patterns of susceptibility of Aspergillus isolates recovered from patients enrolled in the Transplant-Associated Infection Surveillance Network
Baddley JW , Marr KA , Andes DR , Walsh TJ , Kauffman CA , Kontoyiannis DP , Ito JI , Balajee SA , Pappas PG , Moser SA . J Clin Microbiol 2009 47 (10) 3271-5 We analyzed antifungal susceptibilities of 274 clinical Aspergillus isolates from transplant recipients with proven or probable invasive aspergillosis (IA) collected as part of the Transplant Associated Infection Surveillance Network (TRANSNET) and examined the relationship between MIC and 6 or 12-week mortality. Antifungal susceptibility testing was performed by the Clinical and Laboratory Standards Institute (CLSI) M-38A2 broth dilution method for amphotericin B (AMB), itraconazole (ITR), voriconazole (VOR), posaconazole (POS) and ravuconazole (RAV). The isolate collection included 181 A. fumigatus; 28 A. niger; 27 A. flavus; 22 A. terreus, 7 A. versicolor, 5 A. calidoustus; 2 A. nidulans; and 2 isolates identified as Aspergillus spp. Triazole susceptibilities were ≤ 4 microg/ml for most isolates (POS 97.6%; ITR 96.3%; VOR 95.9%; RAV 93.5%). The triazoles were not active against the five A. calidoustus isolates, for which MICs were ≥4microg/ml. AmB inhibited 93.3% of isolates at an MIC of ≤1microg/ml. The exception was A. terreus, for which 15 (68%) of 22 isolates had MICs >1microg/ml. One of 181 isolates of A. fumigatus showed resistance (MIC≥4microg/ml) to 2 of 3 azoles tested. Although there appeared to be a correlation of higher VOR MICs with increased mortality at 6-weeks, the relationship was not statistically significant (R(2)=0.61; p=0.065). Significant relationships of in vitro MIC to all cause mortality at 6 and 12 weeks for VOR or AMB were not found. |
Proteasome inhibitors induce apoptosis in human lung cancer cells through a positive feedback mechanism and the subsequent Mcl-1 protein cleavage
Yuan BZ , Chapman J , Reynolds SH . Oncogene 2009 28 (43) 3775-86 Proteasome inhibitors (PIs) are promising new therapeutic agents for treating non-small cell lung carcinoma (NSCLC). To investigate the mechanisms of action of PIs, we analyzed the proapoptotic activities of PIs (MG132 or Bortezomib) in NSCLC cells. We found that both MG132 (>1 muM) and Bortezomib (>0.025 muM) induced a significant apoptosis in NCI-H1703, a PI-sensitive NSCLC cell line, through initially activating the intrinsic apoptosis pathway, leading to the activation of a positive feedback mechanism (PFM), which then conveyed apoptosis signaling from the intrinsic pathway to the extrinsic pathway with formation of a signaling loop for maximal caspase activation. Mcl-1 and Noxa were identified to be the major anti-apoptotic and proapoptotic proteins, respectively, in PI-induced apoptosis and mutually exclusive in protein stability. Although the Mcl-1 protein was upregulated by proteasome inhibition, it was also subjected to caspase 3-dependent cleavage governed by the PFM. Moreover, it was revealed that Mcl-1 protein cleavage contributed to PFM-governed apoptosis in following inter-related ways: reducing the anti-apoptotic Mcl-1; generating the truncated proapoptotic Mcl-1(S); and inducing a shift of balance between Mcl-1 and Noxa. It was further manifested that tumor necrosis factor-related apoptosis-inducing ligand boosted MG132's proapoptotic activity through strengthening the PFM in both NCI-H1703 and NCI-H358, a PI-resistant NSCLC cell line. Therefore, this study provides a basis for enhancing the efficacy of PIs in treating NSCLC.Oncogene advance online publication, 17 August 2009; doi:10.1038/onc.2009.240. |
Rapid group-, serotype-, and vaccine strain-specific identification of poliovirus isolates by real-time reverse transcription-PCR using degenerate primers and probes containing deoxyinosine residues
Kilpatrick DR , Yang CF , Ching K , Vincent A , Iber J , Campagnoli R , Mandelbaum M , De L , Yang SJ , Nix A , Kew OM . J Clin Microbiol 2009 47 (6) 1939-41 We have adapted our previously described poliovirus diagnostic reverse transcription-PCR (RT-PCR) assays to a real-time RT-PCR (rRT-PCR) format. Our highly specific assays and rRT-PCR reagents are designed for use in the WHO Global Polio Laboratory Network for rapid and large-scale identification of poliovirus field isolates. |
Regional dissemination of KPC-producing Klebsiella pneumoniae
Kitchel B , Sundin DR , Patel JB . Antimicrob Agents Chemother 2009 53 (10) 4511-3 Production of a Klebsiella pneumoniae carbapenemase (KPC) is the most common mechanism of carbapenem resistance in the U.S.; however, until now KPC-producing isolates have not been found in western Michigan. Molecular typing of two KPC-producing K. pneumoniae isolates from Michigan showed their similarity to other Midwestern isolates. They were also unrelated to the dominant sequence type observed throughout the U.S., multilocus sequence type 258. This could represent regional dissemination of another KPC-producing K. pneumoniae strain. |
Repeated rectal SHIVSF162P3 exposures do not consistently induce sustained T cell responses prior to systemic Infection in the repeat-low dose preclinical macaque model
Kersh EN , Luo W , Adams DR , Srinivasan P , Smith JM , Promadej-Lanier N , Ellenberger D , Garcia-Lerma JG , Butera S , Otten R . AIDS Res Hum Retroviruses 2009 25 (9) 905-17 The macaque model of repeated SHIV exposures is increasingly used as a preclinical tool to evaluate biomedical HIV intervention strategies. It is unclear whether multiple virus exposures induce immune responses in macaques, as documented in uninfected individuals repeatedly exposed to HIV. We here address whether repeated, rectal SHIV(SF162P3) exposures lead to systemic T cell activation in 12 rhesus macaques, and whether this is associated with increased infection resistance. Eight macaques became systemically infected after 2-7 exposures, three macaques were less susceptible (infection after 10-12 exposures), and one macaque remained uninfected after 14 exposures. PBMCs were retrospectively monitored for increases in T cell activation by analyzing the proportion of CD8(+) T cells, recently activated or proliferated T cells (markers CD38, Ki67), a marker for cytotoxicity (granzyme B), or T cell-produced plasma cytokines (IFN-gamma, RANTES, IL-2). Repeated virus exposures did not induce sustained, potent, or diverse T cell responses prior to systemic infection. Some changes occurred in the analyzed parameters during repeated virus exposures, but similar T cell activities were also observed in five SHIV-unexposed control macaques. Thus, we found no evidence that delayed infection or resistance to infection was associated with systemic, long-lasting, protective T cell responses to repeated rectal virus exposures. Our results provide further insights into the repeat exposure macaque model. We find that this model can be used for testing biomedical prevention strategies without concern of eliciting a systemic vaccination effect. |
Response of tibialis anterior tendon to a chronic exposure of stretch-shortening cycles: age effects
Ensey JS , Hollander MS , Wu JZ , Kashon ML , Baker BB , Cutlip RG . Biomed Eng Online 2009 8 12 BACKGROUND: The purpose of the current study was to investigate the effects of aging on tendon response to repetitive exposures of stretch-shortening cycles (SSC's). METHODS: The left hind limb from young (3 mo, N = 4) and old (30 mo, N = 9) male Fisher 344 x Brown Norway rats were exposed to 80 maximal SSCs (60 deg/s, 50 deg range of motion) 3 x/week for 4.5 weeks in vivo. After the last exposure, tendons from the tibialis anterior muscle were isolated, stored at -80 degrees C, and then tested using a micro-mechanical testing machine. Deformation of each tendon was evaluated using both relative grip-to-grip displacements and reference marks via a video system. RESULTS: At failure, the young control tendons had higher strain magnitude than the young exposed (p < 0.01) and the old control tendons (p < .0001). Total load at inflection was affected by age only (p < 0.01). Old exposed and control tendons exhibited significantly higher loads at the inflection point than their young counterparts (p < 0.05 for both comparisons). At failure, the old exposed tendons carried higher loads than the young exposed tendons (p < 0.05). Stiffness was affected by age only at failure where the old tendons exhibited higher stiffness in both exposed and control tendons than their young counterparts (p < 0.05 and p < 0.01, respectively). CONCLUSION: The chronic protocol enhanced the elastic stiffness of young tendon and the loads in both the young and old tendons. The old exposed tendons were found to exhibit higher load capacity than their younger counterparts, which differed from our initial hypothesis. |
The science and fiction of emerging rickettsioses
Paddock CD . Ann N Y Acad Sci 2009 1166 133-43 As newly recognized rickettsial diseases and rickettsial pathogens increase in scope and magnitude, several elements related to the concept of emerging rickettsioses deserve consideration. Newly identified rickettsiae may be mildly pathogenic, or perhaps even nonpathogenic, and have little direct impact on human or animal health, yet nonetheless wield considerable influence on the epidemiology and ecology of historically recognized diseases. In this context "new" rickettsioses provide a lens through which "old" rickettsioses are more accurately represented. Predicting pathogen from nonpathogen is not an exact science, particularly as so few rickettsiae have been broadly accepted as nonpathogenic by contemporary rickettsiologists. However, various factors relating to specific physiologic requirements and molecular machinery of the particular rickettsia, as well as characteristics of its invertebrate host that either position or exclude the rickettsia from infecting a human host, must be considered. Close inspection of mild or atypical forms of historically recognized rickettsioses and a greater emphasis on culture- and molecular-based diagnostic techniques are the keys to identifying future rickettsial agents of disease. |
Structural elucidation of isocyanate-peptide adducts using tandem mass spectrometry
Hettick JM , Ruwona TB , Siegel PD . J Am Soc Mass Spectrom 2009 20 (8) 1567-75 Diisocyanates are highly reactive chemical compounds widely used in the manufacture of polyurethanes. Although diisocyanates have been identified as causative agents of allergic respiratory diseases, the specific mechanism by which these diseases occur is largely unknown. To better understand the chemical species produced when isocyanates are reacted with model peptides, tandem mass spectrometry was employed to unambiguously identify the binding site of four commercially-relevant isocyanates on model peptides. In each case, the isocyanates react preferentially with the N-terminus of the peptide. No evidence of side-chain/isocyanate adduct formation exclusive of the N-terminus was observed. However, significant intra-molecular diisocyanate crosslinking was observed between the N-terminal amine and a side-chain amine of arginine, when Arg was located within two residues of the N-terminus. Addition of multiple isocyanates to the peptide occurs via polymerization of the isocyanate at the N-terminus, rather than via addition of multiple isocyanate molecules to varied residues within the peptide. The direct observation of isocyanate binding to the N-terminus of peptides under these experimental conditions is in good agreement with previous studies on the relative reaction rate of isocyanate with amino acid functional groups. |
Attenuated strains of influenza A viruses do not induce degradation of RNA polymerase II
Rodriguez A , Perez-Gonzalez A , Hossain MJ , Chen LM , Rolling T , Perez-Brena P , Donis R , Kochs G , Nieto A . J Virol 2009 83 (21) 11166-74 We have previously shown that infection with laboratory-passaged strains of influenza virus causes both specific degradation of the largest subunit of the RNA polymerase II complex (RNAP II) and inhibition of host cell transcription. When infection with natural human and avian isolates belonging to different antigenic subtypes was examined, we observed that all these viruses efficiently induce the proteolytic process. To evaluate if this process is a general feature of non-attenuated viruses, we studied the behavior of the influenza virus strains A/PR8/8/34 (PR8) and the cold-adapted A/Ann Arbor/6/60 (AA), which are currently used as the donor strains for vaccine seeds due to their attenuated phenotype. We have observed that upon infection with these strains, degradation of the RNAP II does not occur. Moreover, by run-off experiments we observe that PR8 has a reduced ability to inhibit cellular mRNA transcription. In addition, a hyper-virulent PR8 (hvPR8) variant that multiplies much faster than standard PR8 (lvPR8) in infected cells and is more virulent in mice than the parental PR8 virus, efficiently induces RNAP II degradation. Studies with reassortant viruses containing defined genome segments of both hvPR8 and lvPR8 indicate that PA and PB2 subunits individually contribute to the ability of influenza virus to degrade the RNAP II. In addition, recently it has been reported that the inclusion of PA or PB2 from hvPR8 in lvPR8 recombinant viruses, highly increases their pathogenicity. Together, the data indicate that the capacity of the influenza virus to degrade RNAP II and inhibit the host-cell transcription machinery is a feature of influenza A viruses that might contribute to their virulence. |
Closing the gaps between genotype and phenotype in Rickettsia rickettsii
Eremeeva ME , Dasch GA . Ann N Y Acad Sci 2009 1166 12-26 Rocky Mountain spotted fever (RMSF) caused by Rickettsia rickettsii is a severe rickettsiosis that occurs in nearly every state of the continental USA. RMSF is endemic in Central and Southern America, with recent well-documented cases in Mexico, Costa Rica, Panama, Colombia, Brazil, and Argentina. RMSF is the most malignant among known rickettsioses causing severe multiorgan dysfunction and high case fatality rates, which can reach 73% in untreated cases. Variations in pathogenic biotypes of R. rickettsii isolates have been described, and potential correlations of these differences to various clinical manifestations of RMSF have been suggested. We have recently reported on a method of genetic comparison employing sequence differences in intergenic regions (IGR typing) in isolates of R. rickettsii of human, tick, and animal origin. The grouping obtained correlated well with 2 other genotyping systems we have developed, which target the presence and distribution of variable numbers of tandem repeats (TR) and insertion/deletion (INDEL) events. Twenty-five total genotypes of R. rickettsii in 4 primary groups could be distinguished: isolates from Montana, isolates associated with Rhipicephalus sanguineus ticks and human infections in Arizona, other isolates from the USA where Dermacentor variabilis is thought to be the primary vector, and the isolates primarily associated with Amblyomma ticks from Central and South America. In addition, isolate Hlp#2, which is often considered to be a nonpathogenic isolate of R. rickettsii and closely related serotype 364D, exhibited the most diversity from the other isolates compared, and they differ significantly from each other. Because complex interactions underlie the pathogenesis of R. rickettsii in vivo, it is difficult to define the causality of individual events that occur in infected vertebrate hosts and humans. Many microbial factors are likely to contribute to the varied ability of R. rickettsii to cause cellular injury; some of them may also contribute importantly to its virulence for vertebrate hosts and may be linked to the variable genetic markers we have identified. Since circulation of R. rickettsii in nature includes vertical transstadial and transovarial transmission within tick vectors and horizontal passages through vertebrate hosts, it is plausible that isolates of different virulence arose when they became isolated during adaptation to novel vertebrate and tick hosts. Characterization of the physiologically important changes in rickettsial gene expression that occur immediately after tick-to-human or tick-to-animal transitions may require development of new experimental systems. |
Comparative proteomic analysis of antibiotic-sensitive and insensitive isolates of Orientia tsutsugamushi
Chao CC , Garland DL , Dasch GA , Ching WM . Ann N Y Acad Sci 2009 1166 27-37 Scrub typhus, caused by infection with Orientia tsutsugamushi, is probably the most common severe rickettsial disease. Early diagnosis followed by treatment with antibiotics such as doxycycline or chloramphenicol usually quickly decreases fever in patients, and they often recover well from other symptoms of the disease. However, poorly responsive cases have been reported from northern Thailand and southern India. In order to identify protein factors that may be partially responsible for differential drug sensitivity of isolates of Orientia, we compared the protein profiles of doxycycline sensitive (Karp) versus (vs.) insensitive (AFSC4 and AFSC7) isolates. Tryptic peptides from both total water-soluble proteins and from protein spots separated by 2D-PAGE were analyzed using LC-MS/MS. The identity of each protein was established using the published genomic sequence of Boryong strain O. tsutsugamushi. The profiles of protein released into water from these isolates were quite different. There were 10 proteins detected only in AFSC4, 3 only in Karp, and 1 only in AFSC7. Additionally, there were 2 proteins not detected only in AFSC4, 4 not found only in Karp, and 3 not found only in AFSC-7. A comparison of 2D-PAGE protein profiles of drug sensitive strain versus (vs.) insensitive isolates has led to the identification of 14 differentially expressed or localized proteins, including elongation factor Ts and Tu, DNA-directed RNA polymerase alpha-subunit, ATP synthase beta-subunit, and several hypothetical proteins. These data confirm the tremendous proteomic diversity of isolates of Orientia and suggest that drug insensitivity in this species may arise from multiple mechanisms. |
Correlation of cefoxitin MICs with the presence of mecA in Staphylococcus spp
Swenson JM , Brasso WB , Ferraro MJ , Hardy DJ , Knapp CC , Lonsway D , McAllister S , Reller LB , Sader HS , Shortridge D , Skov R , Weinstein MP , Zimmer BL , Patel JB . J Clin Microbiol 2009 47 (6) 1902-5 This report describes the results of an 11-laboratory study to determine if a cefoxitin broth microdilution MIC test could predict the presence of mecA in staphylococci. Using breakpoints of < or = 4 microg/ml for mecA-negative and > or = 6 or 8 microg/ml for mecA-positive isolates, sensitivity and specificity based on mecA or presumed mecA for Staphylococcus aureus at 18 h of incubation were 99.7 to 100% in three cation-adjusted Mueller-Hinton broths tested. For coagulase-negative strains at 24 h of incubation, breakpoints of < or = 2 microg/ml for mecA-negative and > or = 4 microg/ml for mecA-positive isolates gave sensitivity and specificity of 94 to 99% and 69 to 80%, respectively. |
Maternal corticosteroid use and hypospadias
Carmichael SL , Ma C , Werler MM , Olney RS , Shaw GM , National Birth Defects Prevention Study . J Pediatr 2009 155 (1) 39-44, 44 e1 OBJECTIVE: To explore whether women who reported corticosteroid use during pregnancy were more likely to deliver an infant with hypospadias than women who did not. STUDY DESIGN: The analysis encompassed data on deliveries with an estimated due date between 1997 and 2004 from the National Birth Defects Prevention Study, a large population-based, case-control study conducted in the United States. Included were 1165 cases of moderate to severe hypospadias and 3000 nonmalformed male controls. RESULTS: The mothers of 39 cases (3.3%) and 62 controls (2.1%) reported using a corticosteroid medication during the period extending from 4 weeks before conception to 14 weeks after conception. The odds ratio (OR) for any corticosteroid exposure versus no corticosteroid exposure was 1.6 (95% confidence interval [CI] = 1.1 to 2.5); after adjustment for maternal race/ethnicity, education, age, and study site, it was 1.3 (95% CI = 0.8 to 2.0). Analyses by route of administration and specific component suggest that elevated ORs occurred only for nasal spray/inhaled corticosteroids (OR = 1.5; 95% CI = 0.9 to 2.6). CONCLUSIONS: Maternal use of corticosteroid medications was weakly associated with risk of hypospadias, but the association was negligible after adjustment for potential confounders. |
Use of supplements with and without iodine in women of childbearing age in the United States
Gregory CO , Serdula MK , Sullivan KM . Thyroid 2009 19 (9) 1019-20 The iodine status of women of childbearing age in the United States has declined dramatically over the last 25 years (1,2). In fact, using criteria from the World Health Organization, certain subgroups may be classified as iodine deficient (3). Given this dramatic decline in iodine status and the critical role of iodine in fetal neurologic development, in October 2006 the American Thyroid Association recommended iodine supplementation for all pregnant and lactating women in the United States and Canada (4). | We were interested in determining the percentage of women of childbearing age in the United States taking supplements and the percentage taking supplements containing iodine. We looked at data from the National Health and Nutrition Examination Survey (NHANES) for the years 2001–2006. NHANES is a stratified, multistage survey that provides a representative sample of the noninstitutionalized U.S. population (5). Information collected includes the use of any vitamins, minerals, or other dietary supplements within the previous 30 days. Product names are obtained and are compared to a database containing information including vitamin and mineral content. | The reported use of any supplement and use of a supplement containing iodine within the previous 30 days is presented in Table 1 for nonpregnant women of childbearing age (15‱44 years) and pregnant and lactating women. Less than half of nonpregnant women were taking any supplement compared to three fourths of pregnant women and two thirds of lactating women. Only one fifth of nonpregnant and pregnant women and 15% of lactating women were taking a supplement that contained iodine. Although the prevalence of supplement use was much higher among pregnant and lactating women compared to nonpregnant women, the prevalence of taking a supplement containing iodine was similarly low among all groups. This indicates that a lower percentage of supplements consumed by pregnant and lactating women contained iodine compared to supplements consumed by nonpregnant women (26% and 22%, vs. 47%, respectively). |
Hypertensive disorders and severe obstetric morbidity in the United States
Kuklina EV , Ayala C , Callaghan WM . Obstet Gynecol 2009 113 (6) 1299-306 OBJECTIVE: To examine trends in the rates of hypertensive disorders in pregnancy and compare the rates of severe obstetric complications for delivery hospitalizations with and without hypertensive disorders. METHODS: We performed a cross-sectional study using the 1998-2006 Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project. Logistic regressions and population-attributable fractions were used to examine the effect of hypertensive disorders on severe complications. RESULTS: The overall prevalence of hypertensive disorders among delivery hospitalizations increased significantly from 67.2 per 1,000 deliveries in 1998 to 81.4 per 1,000 deliveries in 2006. Compared with hospitalizations without any hypertensive disorders, the risk of severe obstetric complications ranged from 3.3 to 34.8 for hospitalizations with eclampsia/severe preeclampsia and from 1.4 to 2.2 for gestational hypertension. The prevalence of hospitalizations with eclampsia/severe preeclampsia increased moderately from 9.4 to 12.4 per 1,000 deliveries (P for linear trend <0.001) during the period of study. However, these hospitalizations were associated with 38% of hospitalizations with acute renal failure and 19% or more of hospitalizations with ventilation, disseminated intravascular coagulation syndrome, pulmonary edema, puerperal cerebrovascular disorders, and respiratory distress syndrome. Overall, hospitalizations with hypertensive disorders were associated with 57% of hospitalizations with acute renal failure, 27% of hospitalizations with disseminated intravascular coagulation syndrome, and 30% or more of hospitalizations with ventilation, pulmonary edema, puerperal cerebrovascular disorders, and respiratory distress syndrome. CONCLUSION: The number of delivery hospitalizations in the United States with hypertensive disorders in pregnancy is increasing, and these hospitalizations are associated with a substantial burden of severe obstetric morbidity. LEVEL OF EVIDENCE: III. |
Physiological burden associated with the use of filtering facepiece respirators (N95 masks) during pregnancy
Roberge RJ . J Womens Health (Larchmt) 2009 18 (6) 819-26 OBJECTIVE: The purpose of this study was to review the available literature regarding the physiological burden imposed on pregnant women by their wearing filtering facepiece respirators. METHODS: A medical literature search was conducted using MEDLINE (1996-2008) for English language articles, bibliographies of retrieved articles, electronic references from medical and governmental agency sources, and selected textbook articles. RESULTS: Two hundred thirty-four articles from the medical literature and 267 electronic references were retrieved, of which 51 articles from the medical literature, 25 electronic references, and 2 textbook articles were selected for data acquisition. CONCLUSIONS: Very little rigorous scientific data exist on the physiological burden associated with the use of filtering facepiece respirators by pregnant women, and no definitive conclusions can be reached at this time. Although studies are warranted, they may be difficult to undertake because of health concerns and potential liability associated with the use of pregnant women in medical research. Computer modeling that incorporates features of pulmonary function in pregnancy might offer an alternative to human studies. Filtering facepiece respirators developed to meet the respiratory limitations of pregnant wearers might offer a universal design that would improve the comfort and tolerability for all users. Alternative strategies that limit the pregnant woman's contact with potentially infectious agents (e.g., job reassignment, working from home) may have to be employed in certain circumstances. |
Political economy of US states and rates of fatal occupational injury
Loomis D , Schulman MD , Bailer AJ , Stainback K , Wheeler M , Richardson DB , Marshall SW . Am J Public Health 2009 99 (8) 1400-8 OBJECTIVES: We investigated the extent to which the political economy of US states, including the relative power of organized labor, predicts rates of fatal occupational injury. METHODS: We described states' political economies with 6 contextual variables measuring social and political conditions: "right-to-work" laws, union membership density, labor grievance rates, state government debt, unemployment rates, and social wage payments. We obtained data on fatal occupational injuries from the National Traumatic Occupational Fatality surveillance system and population data from the US national census. We used Poisson regression methods to analyze relationships for the years 1980 and 1995. RESULTS: States differed notably with respect to political-economic characteristics and occupational fatality rates, although these characteristics were more homogeneous within rather than between regions. Industry and workforce composition contributed significantly to differences in state injury rates, but political-economic characteristics of states were also significantly associated with injury rates, after adjustment accounting for those factors. CONCLUSIONS: Higher rates of fatal occupational injury were associated with a state policy climate favoring business over labor, with distinct regional clustering of such state policies in the South and Northeast. |
Quartz exposure can cause pneumoconiosis in coal workers
Laney AS , Attfield MD . J Occup Environ Med 2009 51 (8) 867; author reply 868 We read with interest the recent article by McCunney, Morfeld, and Payne entitled What Component of Coal Causes Coal Workers' Pneumoconiosis (CWP)?1 The intent of the article was to identify the specific substance(s) in the underground coal mining environment that are directly responsible for causing CWP. In addressing this question, the authors use a substantial portion of their work to point out that exposure to silica does not likely contribute to CWP. | The authors are not wrong in their assessment of the role of silica in the development of CWP when it occurs at low levels. Epidemiologic studies dating back to the early 1970s showed through modeling of quantitative exposure data that mixed coal mining dust was the primary factor relating to CWP development, whereas silica's role was much smaller.2–4 Anthracite workers in many parts of the world have long been known to suffer high rates of CWP, although anthracite usually contains very low levels of silica. | We believe that by downplaying silica in their desire to seek a more precise explanation for the cause of CWP, the authors have potentially done coal miners a great disservice. There is an important distinction that the authors fail to highlight in their report—silica may not be a major factor in the development of the clinical condition known as CWP, but silica does cause another form of pneumoconiosis among coal workers—silicosis. |
An analysis of injury claims from low-seam coal mines
Gallagher S , Moore S , Dempsey PG . J Safety Res 2009 40 (3) 233-7 INTRODUCTION: The restricted workspace present in low-seam coal mines forces workers to adopt awkward working postures (kneeling and stooping), which place high physical demands on the knee and lower back. METHOD: This article provides an analysis of injury claims for eight mining companies operating low-seam coal mines during calendar years 1996-2008. All cost data were normalized using data on the cost of medical care (MPI) as provided by the U.S. Bureau of Labor Statistics. RESULTS: Results of the analysis indicate that the knee was the body part that led in terms of claim cost ($4.2 million), followed by injuries to the lower back ($2.7 million). While the average cost per injury for these body parts was $13,100 and $14,400, respectively (close to the average cost of an injury overall), the high frequency of these injuries resulted in their preeminence in terms of cost. Analysis of data from individual mining companies suggest that knee and lower back injuries were a consistent problem across companies, as these injuries were each among the top five most costly part of body for seven out of eight companies studied. APPLICATION/IMPACT: Results of this investigation suggest that efforts to reduce the frequency of knee and low back injuries in low-seam mines have the potential to create substantial cost savings. |
Process maps in clinical trial quality assurance
Rosen DH , Johnson S , Kebaabetswe P , Thigpen M , Smith DK . Clin Trials 2009 6 (4) 373-7 BACKGROUND: A process map is a diagram showing the sequential steps and decisions used to accomplish a procedure from start to finish. Process maps are a standard tool in continuous improvement efforts. They have not been used routinely in clinical trials although they are well suited to display trial processes. PURPOSE: We present the use of process maps as a tool to visualize and to monitor the correctness of trial work flows. We show that process maps can be used to assure that trial processes are conducted according to the SOP. METHODS: We describe how a process map is made. We then derive process maps from two sources: the SOP and trial procedures as currently implemented. We compare these maps to each other, using the SOP maps as the gold standard, to check that work is done according to the written procedures. RESULTS: Eight process maps were produced from each source. 172 differences were found between the SOP maps and the walkthrough maps. Differences included the addition of extra steps, order errors, step mistakes, and ambiguities. LIMITATIONS: These process maps focused only on clinic procedures, so interactions with other trial components were not considered. The maps were made after the trial started, which may have biased their content and use. CONCLUSION: Process maps are a simple tool to check if clinical trial processes are operating as designed and offer an effective means to identify and correct such divergences. Further research should focus on using process maps in the design phase of trials, analyzing the cost to benefit ratio for process maps, and linking the analysis of the process map to monitor queries to quantify the improvement gained from using this technique. |
Rapid human immunodeficiency virus (HIV) test quality assurance practices and outcomes among testing sites affiliated with 17 public health departments
Wesolowski LG , Ethridge SF , Martin EG , Cadoff EM , Mackellar DA . J Clin Microbiol 2009 47 (10) 3333-5 Rapid HIV testing is often conducted in non-clinical settings by staff with limited training, so quality assurance (QA) monitoring is critical to ensure accuracy of test results. Rapid tests (n=86,749) were generally conducted according to manufacturer instructions, but ongoing testing competency assessments and on-site QA monitoring were not uniformly conducted. |
The impact of children's emotional and behavioural difficulties on their lives and their use of mental health services
Simpson GA , Cohen RA , Bloom B , Blumberg SJ . Paediatr Perinat Epidemiol 2009 23 (5) 472-81 This paper examines the relationship between the impact of children's emotional and behavioural difficulties and the use of mental health services, using 3 years of nationally representative data from the National Health Interview Survey. Data for the years 2001, 2003 and 2004 were combined (n = 29 265) to identify a sample of 1423 children aged 4-17 years with emotional/behavioural difficulties. Multivariable logistic regression analysis was used. About 5% of U.S. children had emotional or behavioural difficulties. Children whose difficulty was a burden on their family were almost twice as likely to have contact with a mental health professional. Younger children (aged 4-7 years), Hispanic children and non-Hispanic black children with emotional or behavioural difficulties were less likely to use mental health services. These findings indicate that children's emotional and behavioural difficulties influence their lives and those of their families, leading parents to seek help. Racial disparities in mental health service use exist when controlling for the severity and the burden of these difficulties. |
A comparison of drug overdose deaths involving methadone and other opioid analgesics in West Virginia
Paulozzi LJ , Logan JE , Hall AJ , McKinstry E , Kaplan JA , Crosby AE . Addiction 2009 104 (9) 1541-8 AIMS: To describe all people dying from unintentional overdoses of methadone or other opioid analgesics (OOA) in West Virginia in 2006. DESIGN: We analyzed medical examiner data supplemented by data from the state prescription drug monitoring program. We compared people whose deaths involved methadone with those whose deaths involved OOA. FINDINGS: The methadone group included 87 decedents, and the OOA group included 163 decedents. Most were male. Decedents in the methadone group were significantly younger than those in the OOA group: more than a quarter were 18-24 years of age. For both groups, approximately 50% had a history of pain, and 80% had a history of substance abuse. There was no intergroup difference in the prevalence of benzodiazepines at post-mortem. Methadone was significantly less likely to have ever been prescribed than OOA. Among those with prescriptions, the proportion prescribed within 30 days of death was significantly greater for methadone than for hydrocodone, but not for oxycodone. Ten (11.5%) of the methadone decedents were enrolled in an opiate treatment program (OTP) at the time of death. CONCLUSIONS: The high prevalence of a substance abuse history and lack of prescriptions suggest that most of the deaths in both groups are related to substance abuse. There was no indication of a harmful effect from methadone's metabolic interaction with benzodiazepines, but provider or patient unfamiliarity with methadone may have been a risk factor. Prescribing methadone, especially to young males, requires extra care. Providers, OTPs and coroners/medical examiners should use state prescription drug monitoring programs to monitor the use of controlled substances by their patients. |
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- Chronic Diseases and Conditions
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CDC Science Clips is an online, continuously updated, searchable database of scientific literature published by CDC authors. Each article features an Altmetric Attention Score to track social and mainstream media mentions. If you are aware of a CDC-authored publication that does not appear in this database, please let us know.
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